生物活性

• 描述ETC-1002 works as an AMPK activator. ETC-1002 at 100μM increased levels of AMPK phosphorylation in primary human MDMs exposure to LPS, and decreased production of proinflammatory cytokines and chemokines. In dyslipidemic subjects, ETC-1002 not only reduces plasma LDL cholesterol but also significantly attenuates levels of hsCRP, a clinical biomarker of inflammation. Silencing of LKB1 by siRNA could significantly abrogate AMPK phosphorylation and inhibitory effects of ETC-1002 on soluble mediators of inflammation. ETC-1002 suppressed thioglycollate-induced homing of leukocytes into mouse peritoneal cavity in vivo. Also, it restored adipose AMPK activity, reduced JNK phosphorylation, and diminished expression of macrophage-specific marker 4F/80 in a mouse model of diet-induced obesity. ETC-1002 is an investigational drug currently in Phase 2 development for treatment of dyslipidemia and other cardiometabolic risk factors^[2].

• 动物研究
  剂量	Rat: 30 mg/kg[2] (p.o.) Mice: 3 mg/kg - 30 mg/kg[3] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03337308	Hyperlipidemias	Phase 3	Completed	-	United States, Iowa ... more >> PMG Research of McFarland Ames, Iowa, United States, 50010 United States, New Hampshire Foundation Cardiology Nashua, New Hampshire, United States, 03060 United States, North Carolina PMG Research of Piedmont Healthcare Statesville, North Carolina, United States, 28625 PMG Research of Wilmington Wilmington, North Carolina, United States, 28401 United States, Tennessee PMG Research of Knoxville Knoxville, Tennessee, United States, 37912 Collapse <<
  NCT03067441	Hypercholesterolemia ... more >> Atherosclerotic Cardiovascular Disease Collapse <<	Phase 3	Active, not recruiting	December 31, 2019	United States, Florida ... more >> Jedidiah Clinical Research Tampa, Florida, United States, 33607 United States, Kentucky L-MARC Research Center Louisville, Kentucky, United States, 40213 United States, Ohio Sentral Clinical Research Services Cincinnati, Ohio, United States, 45236 Collapse <<
  NCT02988115	Hypercholesterolemia ... more >> Atherosclerotic Cardiovascular Disease Statin Adverse Reaction Collapse <<	Phase 3	Completed	-	United States, Wisconsin ... more >> Kenosha, Wisconsin, United States Collapse <<

• 更多
• 参考文献

• [1] Filippov S, Pinkosky SL, et al. ETC-1002 regulates immune response, leukocyte homing, and adipose tissue inflammation via LKB1-dependent activation of macrophage AMPK. J Lipid Res. 2013 Aug;54(8):2095-108.

  [2] Filippov S, Pinkosky SL, Lister RJ, Pawloski C, Hanselman JC, Cramer CT, Srivastava RAK, Hurley TR, Bradshaw CD, Spahr MA, Newton RS. ETC-1002 regulates immune response, leukocyte homing, and adipose tissue inflammation via LKB1-dependent activation of macrophage AMPK. J Lipid Res. 2013 Aug;54(8):2095-2108. doi: 10.1194/jlr.M035212. Epub 2013 May 24. PMID: 23709692; PMCID: PMC3708360.